PB2190: COMORBIDITIES PREDICT WORSE PROGNOSIS IN PATIENTS WITH POLYCYTHEMIA VERA
Authors: Isidora Arsenović, Jelena Ivanović, Mirjana Cvetkovic, Mihailo Smiljanic, Ljubomir Jakovic, Maja Perunicic Jovanovic, Andrija Bogdanovic, Danijela Lekovic
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by excessive red cell production with increased thrombotic risk and reduced overall survival (OS). Comorbidities were found to influence survival in several hematological malignancies, including primary myelofibrosis, but their effect in PV is not yet defined. Aims: of the study was to evaluate the prevalence and survival impact of comorbidities using the age-adjusted Charlson Comorbidity Index (ACCI) as well as to establish unfavorable risk factors on diagnosis of OS in PV patients. Methods: After the median follow up of 6y among 816 PV patients, 243 deaths were documented (29.8%). We analyzed influence of symptoms: age, gender, laboratory parameters including absolute neutrophilic count (ANC) and lactate dehydrogenase (LDH), history of previous thrombosis, liver and spleen size, ACCI, grade of bone marrow (BM) fibrosis as well as CV risk factors (arterial hypertension, diabetes, smoking attitude and hyperlipidemia). ACCI categorized the severity of comorbidity into three grades: score 1-2 mild, score 3-4 moderate and ≥ 5 severe and incorporates age as correction variable of the final score by adding 1 point for every decade over 50y. Results: Mean age was 62y (range 18-87) with 51.7% male gender and 500pts (61.3%) older than 60y. The mean age of patients who died (70±8.4y) was significantly higher than in living patients (59±12.7y) (p<0.001). According to the standard score (age>60y and/or previous thrombosis), 216 pts (26.5%) were stratified as low risk with median survival 221m while 600 pts (73.5%) as high risk with median survival 119m (p<0.001). ACCI score 0 (without comorbidities) had 96 pts (11.8%) with median survival 233m, score 1-2 (mild grade) had 281 pts (34.4%) with median survival 171m, score 2-3 (moderate grade) 294 pts (36%) with median survival 120m and score ≥5 (severe grade) 145 pts (17.8%) with median survival 84m (p<0.001) (Figure1). Regarding symptoms, pruritus was identified as a favorable, while presence of at least one constitutional symptom as an unfavorable predictor of survival. Univariate analysis identified next risk factors associated with shorter OS: age≥65y(p<0.001), leukocytes ≥15x109/L (p<0.001), ANC ≥10x109/L (p<0.001), platelets ≥1000x109/L (p=0.027), LDH ≥700 U/L (p=0.028), presence of secondary malignancy (p<0.001), BM fibrosis Gr≥1 (p=0.017), previous thrombosis (p=0.03), development of thrombosis during follow up including arterial (p<0.001) and venous (p<0.001). Patients with ACCI score≥4 had significantly higher prevalence rate of development of secondary malignancy (p<0.001). Gender, presence of cytogenetic abnormalities, splenomegaly and hemoglobin (hematocrit) level were not found to have influence on survival. At least one CV risk factor was present in 607 pts (74.3%). Only presence of arterial hypertension showed negative effect on survival (p=0.003). Multivariate Cox regression model revealed that age ≥65y (HR=3.3; p<0.001), ACCI (HR=1.7; p<0.001) and ANC ≥10x109/L (HR=1.6; p=0.001) were the most important predictors of survival. Patients with ACCI score≥4 frequently received hydroxyurea (p<0.001). The mean OS was 12.5y (95% Ci 140-158). The 5y and 10y OS was 81% and 62% respectively. The cause of death was as the follows: cardiomyopathy and heart failure (90 pts; 37%), solid tumor as the second malignancy (37 pts; 15.2%), thrombosis (36 pts; 14.8%), progression to MF or AL (21 pts; 8.6%), COVID infection (10 pts; 4.2) and unknown cause in 49 pts (20.2%). Summary/Conclusion: The application of age-adjusted CCI allows better prognostic assessment by delineating the intermediate risk category and improved identification of the high-risk PV patients with survival less than 8 years.Keywords: Comorbidities, Polycythemia vera, Survival prediction, Myeloproliferative disorder